Ligand substitution reaction mechanism and trans－effect of square－planar complexes

YU Zhao－wen，ZHANG Wu，TENG Hong－mei

（College of Chemistry and Chemical Engineering，Henan University，Kaifeng，475004，Henan，China）

In 1926，CHERNYAEV discovered that the ligand substitution reactions of square planar Pt（II）complexes follow the trans－effect rule；that is，the reactivity of one ligand in the complex is related to the nature of the trans－position ligand.Under the guidance of the trans－effect rule，many novel Pt（II）complexes have been synthesized，and some of them have been found to exhibit antitumor activity［1－4］.This adds to theoretical and practical significance to understand the cause of trans－effect.For this purpose，several theories，includingГРИНБЕРГ’s electrostatic polarization theory，CHATT’sπ－bonding theory，and BENERJEA’s dissociation theory，have been proposed to explain the trans－effect rule［5－7］.Among them，dissociation theory is now rarely mentioned，because it does not conform to the generally accepted association mechanism.Electrostatic polarization theory is only applicable toσ－ligands，whileπ－bond theory is only applicable toπ－ligands andπ－acid ligands.

Considering that trans－effect is a kind of kinetic phenomenon，we think it should be better explained from a kinetic viewpoint.Thus we propose a new theory——ligand repulsion theory to illustrate the transeffect while the reaction mechanism is taken into account.

1 Theoretic basis and proposal of the new theory

The trans－effect strength summarized from a large number of substitution reactions of Pt（II）complexes for common ligands is as follows：

It can be seen from the sequence that the trans－effect strength of the ligands increases with increasing of their softness.Because the softness of ligands is measured by deformability，we can infer that the transeffect strength of the ligands increases with increasing deformability （as toπ－ligands andπ－acid ligands，the inherent deformability and additional deformability owing to the formation ofπ－back bonding must be considered simultaneously）.The correlation between ligands′deformability and their trans－effect is further discussed below.

1.1 Substitution mechanism of square－planar Pt（II）complexes

It is now widely accepted that the substitution reactions of square－planar Pt（II）complexes react by a SN2mechanism［8－14］，and the generally accepted mechanism is outlined in Fig.1［15－16］.

Fig.1 Substitution reaction mechanism of Pt（II）square－planar complexes

We can imagine that，if the reactants are fixed，no matter which ligand is to be replaced，transition state 1 （TS1）is unique，but the intermediate（IM）and transition state 2 （TS2）may have different configurations.Which ligand is to be replaced finally depends mainly on the configurations of IM and TS2.

Then three questions arise：（1）What drives the transformation from TS1to IM？（2）Which ligand is located on the equatorial sites of the trigonal bipyramid of IM？（3）Which ligand is located on the axial site of the tetragonal pyramid of TS2？Answers to these questions are to be discussed below.

1.2 The driving force of the transformation from TS1to IM

As to TS1in Fig.1，the bond electron pair of Pt－Y suffers the repulsions from the other four bond electron pairs.In order to reduce the repulsion according to VSEPR［17］，the tetragonal pyramidal TS1will transform to the trigonal bipyramidal IM spontaneously.That is to say，the repulsion between the bond electron pairs is the driving force for TS1to transform to IM.The existence of some trigonal bipyramidal d8complexes such as［Ni（CN）5］3－，［Pt（SnCl3）5］3－，and Fe（CO）5confirms that the trigonal bipyramidal configuration is more stable than the tetragonal pyramidal one.

1.3 The ligands locating on the equatorial sites of the trigonal bipyramid of IM

It can be concluded from VSEPR［17］that the coordination bond electron pair from a ligand with greater deformability will be closer to the central atom，so its repulsion to the neighboring electron pair will be greater.For example［18］，the bond angle of SCl2（103°）is bigger than that of SF2（98°），and ∠H－C－H（118°）in H2CO is bigger than∠Cl－C－Cl（112°）in COCl2.

In a five－electron－pairs arrangement，i.e.the trigonal bipyramid，there are two different sites：the axial sites and the equatorial sites.The ligands with greater deformability prefer to be located on the equatorial sites.For example［19］，in the configurations of the trigonal bipyramidal fluoride－chlorides of phosphorus（V），the chlorine atom is located on an equatorial site in PClF4，while two chlorine atoms and three chlorine atoms are located on the equatorial sites in PCl2F3and in PCl3F2，respectively.

In principle，the most stable IM should be the one with minimum repulsions among the bond electron pairs，which requires that the three ligands with the greatest deformability are located on the equatorial sites of IM.However，the transformation from TS1to IM is actually a kinetic process；as a result，the ligands can′t rearrange completely.Besides，it is quite easy to change from the tetragonal pyramidal TS1to the trigonal bipyramidal IM，which only needs a couple of trans－position ligands to respectively rotate 30°towards the opposite direction of Y.

As above－mentioned，the trans－effect strength of the ligands increases with the increase of their deformability.If T has the strongest trans－effect，the M－T bond electron pair will be closer to the central atom，and its repulsion to the bond electron pair of the entering ligand Y will be greater as compared with that of anyone of the other three ligands.As a result，Y will shift towards X，exerting agreater repulsion to X and compelling X to leave its original position.Therefore，T，X，and Y will be generally located on the equatorial sites of the trigonal bipyramid of IM.However，in special cases，which ligands are located on the equatorial sites depends on the relative magnitude of the total repulsions of Y suffered，respectively coming from the two couple of trans－position ligands in TS1.If the repulsion of T and X to Y is bigger，T，X and Y will be located on the equatorial sites（Fig.1）；if the repulsion of L and L to Y is bigger，L，L and Y will be located on the equatorial sites.

1.4 The ligand locating on the axial site of the tetragonal pyramid of TS2

Similar to the change from TS1to IM，the change from IM to TS2is also quite easy and it only requires that T and Y respectively rotate 30°towards X （Fig.1）.

It should be noted that the ligands on the axial sites of IM are difficult to shift to the axial site of TS2，since it requires three ligands to rotate simultaneously，two on the equatorial sites of IM respectively rotate 30°，and one on the axial site of IM rotates 90°.That is to say，the ligand on the axial site of TS2must be one of those on the equatorial sites of IM.

Both X and T are possible to locate on the axial site of TS2affording different products.Nevertheless，it should be noted that the ligand on the axial site of TS2not only suffers the repulsion of other four ligands but also suffers the repulsion of the dz2electrons of the central atom.Thus only a ligand with weaker trans－effect is preferably located on this position.Namely，in most cases，X will be located on the axial site of TS2with relatively lower energy.

The entering ligand Y is also possible to locate on the axial site of TS2，if the trans－effect of Y is weaker than that of X.In this case，most IM would come back to the reactants，so the reaction rate will be very slow.

1.5 Ligand repulsion theory

It can be seen from the discussion above that，the trans－effect arises from the repulsions between the bond electron pairs in TS1.In TS1，different ligands give different repulsions to the entering ligand Y.The ligand T with greatest repulsion to Y pushes Y shift to the trans－position of T，leading to the activation of the trans－position ligand.Acordingly，a new theory——ligand repulsion theory，is proposed as follows：（1）the trans－effect of the ligands increases with the increase of their deformability；（2）the larger the deformability of a ligand，the greater its repulsion to the entering ligand is；（3）The equatorial sites of IM are most likely located by the entering ligand Y and a couple of trans－position ligand with bigger repulsion to Y；（4）The ligand on the axial site of TS2is the one on the equatorial sites of IM with weaker trans－effect and it is activated and finally replaced.

2 Explanation of experimental results with ligand repulsion theory

CHEN Rongsan［5］summarized the substitution directions for square planar Pt（II）complexes（Scheme 1）according to the relative trans－effect strength of the four ligands surrounding the Pt（II）ion.The summarizations are listed in the second and the third columns of Table 1.Also presented in the fourth and fifth columns of Table 1are the examples given by us，and the sixth column in this table gives the explanation of ligand repulsion theory.

Scheme 1

Table 1 The substitution direction for square planar Pt（II）complexes according to the relative trans－effect strength of the four ligands

Ligand repulsion theory can give satisfactory explanations for all the situations shown in Table 1.In general，if the strongest trans－effect ligand is determined，the configurations of IM and TS2are determined，so the ligand being replaced is determined（No.1，3，4，5，7，and 8in Table 1）.In some special cases，the synergistic repulsions to the entering ligand from the two couple of trans－position ligands must be considered so as to determine the configurations of IM and TS2and the ligand being replaced（No.2，6，9）.This new theory is advantageous over electrostatic polarization theory andπ－bonding theory，since they are difficult to explain the situations of No.2and No.6，why the replaced ligand is not the ammonia with the weakest trans－effect，and the situation of No.9is much more difficult to be understood by the old theory.

Ligand repulsion theory and electrostatic polarization theory have some similarity，since they all cover the polarization effect of the central ion to the ligands.However，electrostatic polarization theory is concerned about the weakening of trans－position bond by the polarization effect（a kind of thermodynamic consideration），while ligand repulsion theory is concerned about the influence of polarization effect on the configuration of intermediate（a kind of kinetic consideration）.

［1］ROSENBERG B，VANCAMP L，TROSKO J E，et al.Platinum compounds：a new class of potent antitumour agents［J］.Nature，1969，222：385－386.

［2］WONG E，GIANDOMENICO C M.The interactions of low oxidation state transition metal［J］.Chem Rev，1999，99：2451－2466.

［3］PANTOJA E，GALLIPOLI A，van ZUTPHENA S，et al.In vitro antitumor activity and interaction with DNA model bases ofcis－［PtCl2（iPram）（azole）］complexes and comparison with their trans analogues［J］.Inorganica Chimica Acta，2006，359（13）：4335－4342.

［4］van RIJT S，van ZUTPHEN S D H，BROUWER J，et al.Structure－activity relationship studies for three new asymmetriccis－platinum（II）aminoethanol－based complexes［J］.Inorganica Chimica Acta，2006，359（12）：4125－4129.

［5］陈荣三.金属络合物中的反位效应 ［J］.化学通报，1965（8）：474－479.

［6］CHATT J，DUNCANSON L A，VENANZI L M.Directing effects in inorganic substitution reactions.Part I.A hypothesis to explain the trans－effect［J］.J Chem Soc，1955，4456－4460.

［7］BENERJEA D，BASOLO F，PEARSON R G.Mechanism of some substitution reactions of complex ions.Ⅻ.Reactions of some platinum（Ⅱ）complexes with various reactants［J］.J Am Chem Soc，1957，79：4055.

［8］FEKL U，van ELDIK R.Specific chelate tuning of the substitution kinetics of platinum（II）complexes in aqueous solution［J］.Eur J Inorg Chem，1998：389－396.

［9］WEBER C F，van ELDIK R.Influence of solvent on ligand－substitution reactions of PtII complexes as function of the acceptor properties of the spectator chelate［J］.Eur J Inorg Chem，2005：4755－4761.

［10］JAGANYI D，MUNISAMY V M，REDDY D.Role of bridging diamine linkers on the rate of ligand substitution in a series of dinuclear PtⅡcomplexes［J］.Intern J Chem Kinet，2006，38：202－210.

［11］KARMAKAR P，MALLICK S，MONDAL S，et al.Kinetics and mechanism of the interaction of adenosine withcis－diaqua（cis－1，2－diaminocyclohexane）platinum（II）perchlorate in aqueous medium ［J］.Intern J Chem Kinet，2011，43：219－229.

［12］MAMBANDA A，JAGANYI D，HOCKREUTHER S，et al.Tuning the reactivity of chelated dinuclear Pt（II）complexes through a flexible diamine linker.A detailed kinetic and mechanistic study［J］.Dalton Trans，2010，39：3595－3608.

［13］MAMBANDA A，JAGANYI D.A kinetics and mechanistic study on the role of the structural rigidity of the linker on the substitution reactions of chelated dinuclear Pt（II）complexes［J］.Dalton Trans，2012，41：908－920.

［14］ONGOMA P，JAGANYI D.Theπ－acceptor effect in the substitution reactions of tridentate N－donor ligand complexes of platinum（II）：a detailed kinetic and mechanistic study［J］.Dalton Trans，2012，41：10724－10730.

［15］项斯芬.无机化学新兴领域导论［M］.北京：北京大学出版社，1988：152－163.

［16］章 慧.配位化学——原理与应用［M］.北京：化学工业出版社，2008：344－345.

［17］GILLESPIE R J，NYHOLM R S.Inorganic stereochemistry［J］.Q Rev Chem Soc，1957，11：339－380.

［18］HARGITTAI I.Space concept in chemistry［J］.Pure Appl Chem，1992，64（10）：1489－1498.

［19］GILLESPIE R J，ROBINSON E A.Models of molecular geometry［J］.Chem Soc Rev，2005，34：396－407.